外源性一氧化碳释放分子2对严重烧伤小鼠肝脏炎性反应的抑制作用

The inhibitory effects of extrinsic carbon monoxide-releasing moleculesⅡon inflammatory responses in liver of mice with severe burns

目的观察外源性一氧化碳释放分子2(CORM-2)对严重烧伤小鼠肝脏炎性反应的抑制作用,并探讨其机制。方法将C_(57)BL/6小鼠随机分成假伤组(模拟烧伤)、假伤+CORM-2组、烧伤组、烧伤+CORM-2组及烧伤+二甲亚砜(DMSO)组,每组9只。假伤+CORM-2组除伤后使用CORM-2以外,其他处理同假伤组。烧伤+CORM-2组及烧伤+DMSO组除伤后分别使用CORM-2、DMSO外,其余处理同烧伤组。于伤后24 h检测小鼠血清丙氨酸转氨酶(ALT)及天冬氨酸转氨酶(AST)的水平,肝组织髓过氧化物酶(MPO)及核因子κB(NF-κB)活性,胞间黏附分子1(ICAM-1)和血管细胞黏附分子1(VCAM-1)蛋白的表达;检测各组小鼠肝窦内皮细胞(HSEC)经各自血清刺激后对中性粒细胞(PMN)的黏附作用。结果与假伤组比较,烧伤组小鼠血清ALT、AST的水平[(398±34)、(122±22)U/L]及肝组织MPO活性、肝组织ICAM-1和VCAM-1蛋白表达水平均明显升高(P<0.05或P<0.01)。与烧伤组比较,烧伤+CORM-2组上述情况明显改善,且NF-κB活性下降。与假伤组比较,烧伤组小鼠HSEC对PMN的黏附作用增强;烧伤+CORM-2组该作用明显弱于烧伤组(P<0.05)。结论外源性CORM-2能明显抑制肝组织NF-κB活性,减少ICAM-1、VCAM-1蛋白的表达水平,减轻严重烧伤后组织中白细胞滞留,改善肝功能,可有效减轻肝脏炎性反应。

To investigate the inhibitory effects of extrinsic carbon monoxide-releasing molecules 11 on inflammatory responses in liver of mice with severe burns and its potential mechanisms. Methods Forty-five male C57BL/6 mice were randomly divided into sham（simulation of burn with 37℃ warm warter） , sham ＋ CORM-2 （with 8 mg/kg CROM-2 after the same manipulation as sham group） ,burn （with 15% TBSA full-thickness burns） ,burn ＋ CORM-2 （with 8 mg/kg CROM-2 after the same manipulation as burn group） ,burn ＋ DMSO （with DMSO after the same treatment as burn group） groups, with 9 mice in each group. The serum level of ALT and AST were determined at 24 post-burn hours （PBH） ,and the level of myeloperoxidase （MPO） , nuclear factor（NF） KB ,intercellular adhesion molecular （ ICAM-1 ） ,vascular cell adhesion molecular（ VCAM-1 ） ,as well as adhesion of polymorphonuclear leucocytes to sinusoidal endothelial cells （HSECs） after serum stimulation were detected and assessed at the same time-points. Results The level of ALT and AST（398 ±34,122 ± 22 ） ,the activity of MPO and NF-kB ,the protein level of ICAM-1 and VCAM-1 in burn group were obviously increased when compared with those in sham group and burn ＋ CROM-2 group（ P 〈 0.05 or P 〈 0.01 ）. Additionally, the adhesion of PMN on HSEC after stimulation of serum in burn group was enhanced, while it was markedly inhibited after stimulation of serum in burn ＋ CORM-2 group（ P 〈 0.05）. Conclusion Extrinsic CORM-2 exhibits the ability to inhibit NF-KB activity,reduces the hepatic expression of ICAM-1 and VCAM-1 ,thereby alleviating sequestration of leukocytes after severe burns, so that henatic inflammatory resnonse is ameliorated, and liver functinn is improved.